The Burning Question

ChE Seniors Use Microfluidics to Study Why Cancer Spreads

October 31, 2018

BATON ROUGE, LA – The first question that undoubtedly comes to mind when someone is
told they have cancer is “why?” This is the very question LSU College of Engineering
students are asking when it comes to breast cancer metastasis.

Why do cancer cells spread? In order to fix a problem, you must first know the cause,
and that is exactly what LSU Chemical Engineering (ChE) seniors Josh Campbell and
Amy Morgan are trying to determine.

For the past two years, Campbell and Morgan have worked in LSU ChE Professor Adam
Melvin’s Microfluidics Lab to create a 3D environment for breast cancer cells to see
what causes their migration to other organs, where they form a metastatic tumor.

“We want to understand why breast cancer cells migrate in the way they do,” said Morgan,
a native of Broussard, La. “We want to understand why the cells detach from the tumor,
travel through the bloodstream, exit the bloodstream, and grow a new tumor in another
part of the body. You can’t really figure out how to fix something if you don’t understand
the problem. So, we must figure out the problem first.”

In their initial study, Campbell and Morgan both studied chemotaxis—the migration
of cancer cells due to a chemical gradient—using a three-channel microfluidic device
to create a gradient that showed which direction the cells would travel.

After working side by side for a year, the pair split up their research with Campbell
continuing to study chemotaxis and Morgan concentrating on migration in response to
a stiffness gradient, known as durotaxis. While current studies of durotaxis are limited
to 2D, Morgan’s research focuses on creating a 3D environment with durotactic cues
similar to what cells would experience within the body.

“Durotaxis is the migration of cancer cells due to some sort of stiffness gradient
within the extracellular matrix, which would be caused by polymers of varying rigidity
within the matrix,” Morgan said.

Morgan used the same microfluidic device used in chemotaxis, except she and LSU ChE
Professor Kevin McPeak created microfabricated structures within the device that cause
the collagen to have stiffness gradients.

“Dr. McPeak specializes in wet etching,” Morgan said. “So, what we do is develop a
silicon wafer, give it to Dr. McPeak to expose to KOH [potassium hydroxide], then
it etches certain planes away based on the crystal structure, creating unique geometries
like wedges or pyramids. Then, we’re able to see how the cells migrate within the
device—if they move to or away from the gradient. We would expect them to move toward
it. For example, the tumor would be the stiffer tissue within the body, so you would
expect to see the surrounding cells migrating toward it.”

Video taken over a 14-hour period shows the cells traveling preferentially around
the pyramids, meaning they want to travel to the stiffest gradient of the collagen.
While this may not sound like much, understanding what the cells are doing and how
they act is one step closer to improving treatment for metastatic cancer cases.

“We’re part of the earlier part of the solution because we’re just trying to understand
what exactly is happening in the body,” Morgan said. “The more you know about a problem,
the better chance you have of coming up with solutions.”

For Campbell’s project, he developed an orthogonal device that will allow researchers
to create and study competing chemical gradients as opposed to just one. Using this
device, one can create “flow-free” chemical gradients within a chamber seeded with
triple-negative breast cancer cells in a 3D collagen matrix to see if cells are preferentially
drawn to certain proteins.“We make a chemical gradient by flowing fluid through one side and having a buffer
on the other side,” he said. “The middle is where the cells are, so that’s where you
get the concentration gradients of certain proteins.”

As for why he and Morgan use triple-negative breast cancer cells in their research,
Campbell says they are the most metastatic and highly migratory, which makes it easier
to see them move.

“They are also the ones that are hardest to treat with traditional medication,” he
added.

“It only takes one cell to decide to leave and travel to another spot,” Morgan said
of metastasis. “What has always interested me is how these cells are so easy to kill
in the lab. We have to be careful to not contaminate anything and keep the cells at
body temperature. The body is their happy place, so we try to mimic that.”

Morgan says in order to work on one project for years, there must be some motivation
behind doing it.

“It’s a lot of work, and a lot of times it doesn’t work the way you want it to, so
you definitely need to have that motivation that comes from somewhere else other than,
‘It’s just a job,’” she said.

“I think that’s just how research is, right?” Campbell said. “Trying to figure out
new things, and people haven’t really done this research before, so I think things
not always working out as you expect is part of the research process.”

As for researching a topic that has such grim statistics—only 27 percent of women
with metastatic breast cancer will live longer than five years after diagnosis—the
students remain hopeful that their work will support the researchers after them who
may be able to improve treatment.

“It’s really been an eye-opening project,” Morgan said. “A few of my aunts had cancer,
one of which was metastatic, so to be able to understand what causes metastatic cancer
and why cells do the things they do, as well as knowing that I’m a part of something
that will one day be able to make a difference, I really enjoy that aspect of it.”